Germline mutation in the NBR1 gene involved in autophagy detected in a family with renal tumors

Adolphe, Florine; Ferlicot, Sophie; Verkarre, Virginie; Posseme, Katia; Couvé, Sophie; Garnier, Pauline; Droin, Nathalie; Deloger, Marc; Job, Bastien; Giraud, Sophie; Paillerets, Brigitte Bressac‐de; Gardie, Betty; Richard, Stéphane; Renaud, Flore; Gad, Sophie

doi:10.1016/j.cancergen.2021.07.003

Cited by 6 publications

(4 citation statements)

References 24 publications

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“…Multiple other genes have been reported to potentially predispose to RCC, including PBRM1, BRIP1, CDKN2B, DCLRE1B/ Apollo, MITF and NBR1, but are not routinely tested in clinical practice as they appear to be rare causes of inherited RCC/MPRT and/or require additional confirmation of RCC risks [36][37][38][39][40]. Several genes listed in Table 1, such as VHL, SDHx and FH are associated with predisposition (to varying extents) to both RCC and PPGL.…”

Section: Discussionmentioning

confidence: 99%

Characteristics, aetiology and implications for management of multiple primary renal tumours: a systematic review

Zhang,

Andreou,

Bhatt

et al. 2024

Eur J Hum Genet

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In a subset of patients with renal tumours, multiple primary lesions may occur. Predisposition to multiple primary renal tumours (MPRT) is a well-recognised feature of some inherited renal cancer syndromes. The diagnosis of MPRT should therefore provoke a thorough assessment for clinical and genetic evidence of disorders associated with predisposition to renal tumourigenesis. To better define the clinical and genetic characteristics of MPRT, a systematic literature review was performed for publications up to 3 April 2024. A total of 7689 patients from 467 articles were identified with MPRT. Compared to all patients with renal cell carcinoma (RCC), patients with MPRT were more likely to be male (71.8% versus 63%) and have an earlier age at diagnosis (<46 years, 32.4% versus 19%). In 61.1% of cases MPRT were synchronous. The proportion of cases with similar histology and the proportion of cases with multiple papillary renal cell carcinoma (RCC) (16.1%) were higher than expected. In total, 14.9% of patients with MPRT had a family history of cancer or were diagnosed with a hereditary RCC associated syndrome with von Hippel-Lindau (VHL) disease being the most common one (69.7%), followed by Birt-Hogg-Dubé (BHD) syndrome (14.2%). Individuals with a known or likely genetic cause were, on average, younger (43.9 years versus 57.1 years). In rare cases intrarenal metastatic RCC can phenocopy MPRT. We review potential genetic causes of MPRT and their implications for management, suggest an approach to genetic testing for individuals presenting with MPRT and considerations in cases in which routine germline genetic testing does not provide a diagnosis.

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Section: Discussionmentioning

confidence: 99%

Characteristics, aetiology and implications for management of multiple primary renal tumours: a systematic review

Zhang,

Andreou,

Bhatt

et al. 2024

Eur J Hum Genet

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“…In addition to the NBR1 mRNA expression found in most cancers, it was associated with low cancer specificity (35,36). NBR1 overexpression increased the proliferation of renal cancer cells in vitro (37) and promoted tumor metastasis in a breast cancer mouse model (38). In contrast, the knockdown of NBR1 inhibits in vitro cell migration (39) suggesting that NBR1 is involved in cancer development.…”

Section: Discussion/conclusionmentioning

confidence: 99%

Targeting PPT1 with ezurpimtrostat sensitives liver tumor to immunotherapy by switching cold into hot microenvironments

Bestion

Rachid

Tijeras‐Raballand³

et al. 2023

Preprint

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Background: Palmitoyl-protein thioesterase-1 (PPT1) is an exciting druggable target for inhibiting autophagy in cancer. Methods: In this study, we aimed to evaluate the effects of ezurpimtrostat-targeting PPT1 in combination with an anti-PD-1 antibody in liver cancer using a transgenic immunocompetent mouse model. Results: Herein, we revealed that inhibition of PPT1 using ezurpimtrostat, a safe anticancer drug in humans, decreased the liver tumor burden by inducing the penetration of lymphocytes within tumors when combined with anti-programmed death-1 (PD-1). Inhibition of PPT1 potentiates the effects of anti-PD-1 immunotherapy by increasing the expression of major histocompatibility complex (MHC)-I at the surface of liver cancer cells and modulates immunity through recolonization and activation of cytotoxic CD8+ lymphocytes. Conclusions: Ezurpimtrostat turns cold into hot tumors and, thus, constitutes a powerful strategy to improve T cell-mediated immunotherapies in liver cancer.

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“…There are a number of "novel" RCC-associated genes: PRDM10, ELOC1/TFEB1, NBR1, etc. However, virtually all relevant reports are generally limited by the description of single pedigrees; therefore, the population-based significance of these findings remains to be clarified [72,[169][170][171][172].…”

Section: Other Hereditary Cancer Syndromes Associated With Increased ...mentioning

confidence: 99%

Hereditary Renal Cancer Syndromes

Yanus,

Kuligina,

Imyanitov

2024

Medical Sciences

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Familial kidney tumors represent a rare variety of hereditary cancer syndromes, although systematic gene sequencing studies revealed that as many as 5% of renal cell carcinomas (RCCs) are associated with germline pathogenic variants (PVs). Most instances of RCC predisposition are attributed to the loss-of-function mutations in tumor suppressor genes, which drive the malignant progression via somatic inactivation of the remaining allele. These syndromes almost always have extrarenal manifestations, for example, von Hippel–Lindau (VHL) disease, fumarate hydratase tumor predisposition syndrome (FHTPS), Birt–Hogg–Dubé (BHD) syndrome, tuberous sclerosis (TS), etc. In contrast to the above conditions, hereditary papillary renal cell carcinoma syndrome (HPRCC) is caused by activating mutations in the MET oncogene and affects only the kidneys. Recent years have been characterized by remarkable progress in the development of targeted therapies for hereditary RCCs. The HIF2aplha inhibitor belzutifan demonstrated high clinical efficacy towards VHL-associated RCCs. mTOR downregulation provides significant benefits to patients with tuberous sclerosis. MET inhibitors hold promise for the treatment of HPRCC. Systematic gene sequencing studies have the potential to identify novel RCC-predisposing genes, especially when applied to yet unstudied populations.

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Germline mutation in the NBR1 gene involved in autophagy detected in a family with renal tumors

Cited by 6 publications

References 24 publications

Characteristics, aetiology and implications for management of multiple primary renal tumours: a systematic review

Characteristics, aetiology and implications for management of multiple primary renal tumours: a systematic review

Targeting PPT1 with ezurpimtrostat sensitives liver tumor to immunotherapy by switching cold into hot microenvironments

Hereditary Renal Cancer Syndromes

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